title: Tlx3 controls cholinergic transmitter and Peptide phenotypes in a subset of prenatal sympathetic neurons.
abstract: The embryonic sympathetic nervous system consists of predominantly noradrenergic neurons and a very small population of cholinergic neurons. Postnatal development further allows target-dependent switch of a subset of noradrenergic neurons into cholinergic phenotype. How embryonic cholinergic neurons are specified at the prenatal stages remains largely unknown. In this study, we found that the expression of transcription factor Tlx3 was progressively restricted to a small population of embryonic sympathetic neurons in mice. Immunostaining for vesicular acetylcholine transporter (VAChT) showed that Tlx3 was highly expressed in cholinergic neurons at the late embryonic stage E18.5. Deletion of Tlx3 resulted in the loss of Vacht expression at E18.5 but not E12.5. By contrast, Tlx3 was required for expression of the cholinergic peptide vasoactive intestinal polypeptide (VIP), and somatostatin (SOM) at both E12.5 and E18.5. Furthermore, we found that, at E18.5 these putative cholinergic neurons expressed glial cell line-derived neurotrophic factor family coreceptor Ret but not tyrosine hydroxylase (Ret(+)/TH(-)). Deletion of Tlx3 also resulted in disappearance of high-level Ret expression. Last, unlike Tlx3, Ret was required for the expression of VIP and SOM at E18.5 but not E12.5. Together, these results indicate that transcription factor Tlx3 is required for the acquisition of cholinergic phenotype at the late embryonic stage as well as the expression and maintenance of cholinergic peptides VIP and SOM throughout prenatal development of mouse sympathetic neurons.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Huang
authors.forename: Jia
authors.initials: J
authors.lastname: Hu
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Yanzhen
authors.initials: Y
authors.lastname: Nie
authors.forename: Junlan
authors.initials: J
authors.lastname: Geng
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002452:Cell Count; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011247:Pregnancy; D051096:Proto-Oncogene Proteins c-ret / Q000096:biosynthesis / Q000235:genetics; D013004:Somatostatin / Q000235:genetics / Q000502:physiology; D013233:Stellate Ganglion / Q000166:cytology / Q000254:growth & development; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C493460:Slc18a3 protein, mouse; C487377:Tlx3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D014446:Tyrosine 3-Monooxygenase; D051096:Proto-Oncogene Proteins c-ret